Skip to main content
SpringerLink
Log in

A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

An Erratum to this article was published on 23 November 2007

Abstract

Rationale

Few randomized, placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder.

Objectives

The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release (ER) with placebo in treating panic disorder. Secondary objectives included comparing paroxetine with venlafaxine ER and placebo.

Methods

Outpatients aged ≥18 years (placebo, n = 157; venlafaxine ER 75 mg, n = 156; venlafaxine ER 225 mg, n = 160; paroxetine, n = 151), with a primary diagnosis of panic disorder (±agoraphobia) based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for ≥3 months were randomly assigned to receive venlafaxine ER (titrated to 75 mg/day or 225 mg/day), paroxetine (titrated to 40 mg/day), or placebo for 12 weeks. The primary efficacy measure was the percentage of patients free of full-symptom panic attacks (≥ four symptoms) at endpoint. Key secondary outcomes included the Panic Disorder Severity Scale (PDSS) mean score change and response.

Results

At endpoint, all active treatment groups showed a significantly (P < 0.01) greater proportion of patients free of full-symptom panic attacks, compared with placebo, and were superior (P < 0.05) on most secondary measures. The venlafaxine ER 225 mg group had significantly (P < 0.05) greater mean PDSS score improvement than the paroxetine group (−12.58 vs −11.87) and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%). Both drugs were generally well tolerated.

Conclusion

Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Allgulander C, Hackett D, Salinas E (2001) Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Br J Psychiatry 179:15–22

    Article  PubMed  CAS  Google Scholar 

  • Allgulander C, Mangano R, Zhang J, Dahl AA, Lepola U, Sjodin I, Emilien G (2004) Efficacy of venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine. Hum Psychopharmacol 19:387–396

    Article  PubMed  CAS  Google Scholar 

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM-IV), 4th edn (revised). Washington, DC

  • American Psychiatric Association (1998) Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. Am J Psychiatry 155:1–34

    Google Scholar 

  • Baldwin DS,Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Wittchen HU, British Association for Psychopharmacology (2005) Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 19:567–596

    Article  PubMed  CAS  Google Scholar 

  • Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Baldwin DS, den Boer JA, Kasper S, Shear MK (1998a) Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 59:47–54

    PubMed  Google Scholar 

  • Ballenger JC, Wheadon DE, Steiner M, Bushnell W, Gergel IP (1998b) Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Am J Psychiatry 155:36–42

    PubMed  CAS  Google Scholar 

  • Barlow D, Gorman J, Shear M, Woods S (2000) Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA 283:2529–2536

    Article  PubMed  CAS  Google Scholar 

  • Bertani A, Perna G, Migliarese G, Di Pasquale D, Cucchi M, Caldirola D, Bellodi L (2004) Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study. Pharmacopsychiatry 37:206–210

    Article  PubMed  CAS  Google Scholar 

  • Black DW, Wesner R, Bowers W, Gabel J (1993) A comparison of fluvoxamine, cognitive therapy, and placebo in the treatment of panic disorder. Arch Gen Psychiatry 50:44–50

    PubMed  CAS  Google Scholar 

  • Bradwejn J, Ahokas A, Stein DJ, Salinas E, Emilien G, Whitaker T (2005) Venlafaxine extended-release capsules in panic disorder: Flexible-dose, double-blind, placebo-controlled study. Br J Psychiatry 187:352–359

    Article  PubMed  Google Scholar 

  • Dannon PN, Iancu I, Grunhaus L (2002) The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Hum Psychopharmacol 17:329–333

    Article  PubMed  CAS  Google Scholar 

  • Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P (2007) Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol 10:51–61

    Article  PubMed  CAS  Google Scholar 

  • Gelenberg AJ, Lydiard RB, Rudolph RL, Aguiar L, Haskins JT, Salinas E (2000) Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. JAMA 283:3082–3088

    Article  PubMed  CAS  Google Scholar 

  • Geracioti TD Jr (1995) Venlafaxine treatment of panic disorder: a case series. J Clin Psychiatry 56:408–410

    PubMed  Google Scholar 

  • Gilmor ML, Owens MJ, Nemeroff CB (2002) Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry 159:1702–1710

    Article  PubMed  Google Scholar 

  • Goodwin RD, Faravelli C, Rosi S, Cosci F, Truglia E, de Graaf R, Wittchen HU (2005) The epidemiology of panic disorder and agoraphobia in Europe. Eur Neuropsychopharmacol 15(4):435–443

    Article  PubMed  CAS  Google Scholar 

  • Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505

    Article  PubMed  CAS  Google Scholar 

  • Guy W (ed) (1976) ECDEU Assessment Manual for Psychopharmacology (revised). National Institute of Mental Health, Psychopharmacology Research Branch, Rockville, MD

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    PubMed  CAS  Google Scholar 

  • Hochberg Y (1988) A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75:800–809

    Article  Google Scholar 

  • Johnson MR, Lydiard RB, Ballenger JC (1995) Panic disorder. Pathophysiology and drug treatment. Drugs 49:328–344

    PubMed  CAS  Google Scholar 

  • Katschnig H, Amering M, Stolk JM, Klerman GL, Ballenger JC, Briggs A, Buller R, Cassano G, Garvey M, Roth M (1995) Long-term follow-up after a drug trial for panic disorder. Br J Psychiatry 167:487–494

    PubMed  CAS  Google Scholar 

  • Kelsey JE (1996) Dose-response relationship with venlafaxine. J Clin Psychopharmacol 16:21S–26S

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, Chiu WT, Jin R, Ruscio AM, Shear K, Walters EE (2006) The epidemiology of panic attacks, panic disorder, and agoraphobia in the national comorbidity survey replication. Arch Gen Psychiatry 63:415–424

    Article  PubMed  Google Scholar 

  • Khan A, Upton GV, Rudolph RL, Entsuah R, Leventer SM (1998) The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group. J Clin Psychopharmacol 18:19–25

    Article  PubMed  CAS  Google Scholar 

  • Koch S, Hemrick-Luecke SK, Thompson LK, Evans DC, Threlkeld PG, Nelson DL, Perry KW, Bymaster FP (2003) Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology 45:935–944

    Article  PubMed  CAS  Google Scholar 

  • Liebowitz MR, Asnis G, Tzanis E, Whitaker T (2004) A double-blind, placebo-controlled trial of venlafaxine XR in the short-term treatment of panic disorder [abstract]. Eur Neuropsychopharmacol 14(Suppl 3):S305–S306

    Article  Google Scholar 

  • Liebowitz MR, Gelenberg AJ, Munjack D (2005a) Venlafaxine vs paroxetine in social anxiety disorder. Arch Gen Psychiatry 62:190–198

    Article  PubMed  CAS  Google Scholar 

  • Liebowitz MR, Mangano RM, Bradwejn J, Asnis G (2005b) A Randomized controlled trial of venlafaxine extended release in generalized social anxiety disorder. J Clin Psychiatry 66:238–247

    PubMed  CAS  Google Scholar 

  • Londborg PD, Wolkow R, Smith WT, DuBoff E, England D, Ferguson J, Rosenthal M, Weise C (1998) Sertraline in the treatment of panic disorder. A multi-site, double-blind, placebo-controlled, fixed-dose investigation. Br J Psychiatry 173:54–60

    PubMed  CAS  Google Scholar 

  • Lydiard RB (1987) Desipramine in agoraphobia with panic attacks: an open, fixed-dose study. J Clin Psychopharmacol 7:258–260

    PubMed  CAS  Google Scholar 

  • Markowitz JS, Weissman MM, Ouellette R, Lish JD, Klerman GL (1989) Quality of life in panic disorder. Arch Gen Psychiatry 46:984–992

    PubMed  CAS  Google Scholar 

  • Michelson D, Lydiard RB, Pollack MH, Tamura RN, Hoog SL, Tepner R, Demitrack MA, Tollefson GD (1998) Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Am J Psychiatry 155:1570–1577

    PubMed  CAS  Google Scholar 

  • Michelson D, Pollack M, Lydiard RB, Tamura R, Tepner R, Tollefson G (1999) Continuing treatment of panic disorder after acute response: randomised, placebo-controlled trial with fluoxetine. The Fluoxetine Panic Disorder Study Group. Br J Psychiatry 174:213–218

    PubMed  CAS  Google Scholar 

  • Michelson D, Allgulander C, Dantendorfer K, Knezevic A, Maierhofer D, Micev V, Paunovic VR, Timotijevic I, Sarkar N, Skoglund L, Pemberton SC (2001) Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. Br J Psychiatry 179:514–518

    Article  PubMed  CAS  Google Scholar 

  • Oehrberg S, Christiansen PE, Behnke K, Borup AL, Severin B, Soegaard J, Calberg H, Judge R, Ohrstrom JK, Manniche PM (1995) Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled study. Br J Psychiatry 167:374–379

    PubMed  CAS  Google Scholar 

  • Papp LA, Sinha SS, Martinez JM, Coplan JD, Amchin J, Gorman JM (1998) Low-dose venlafaxine treatment in panic disorder. Psychopharmacol Bull 34:207–209

    PubMed  CAS  Google Scholar 

  • Perna G, Bertani A, Caldirola D, Di Pasquale D, Migliarese G, Bellodi L (2004) Modulation of hyperreactivity to 35% CO2 after one week of treatment with paroxetine and reboxetine: a double-blind, randomized study. J Clin Psychopharmacol 24:277–282

    Article  Google Scholar 

  • Pollack MH, Worthington JJ, Otto MW, Maki KM, Smoller JW, Manfro GG, Rudolph R, Rosenbaum JF (1996) Venlafaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacol Bull 32:667–670

    PubMed  CAS  Google Scholar 

  • Pollack MH, Otto MW, Worthington JJ, Manfro GG, Wolkow R (1998) Sertraline in the treatment of panic disorder: a flexible-dose multicenter trial. Arch Gen Psychiatry 55:1010–1016

    Article  PubMed  CAS  Google Scholar 

  • Pollack MH, Allgulander C, Bandelow B, Cassano GB, Greist JH, Hollander E, Nutt DJ, Okasha A, Swinson RP (2003) WCA recommendations for the long-term treatment of panic disorder. CNS Spectr 8:17–30

    PubMed  Google Scholar 

  • Pollack MH, Lepola U, Koponen H, Simon NM, Worthington JJ, Emilien G, Tzanis E, Salinas, E, Whitaker T, Gao B (2007) A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. Depress Anxiety 24:1–14

    Article  PubMed  CAS  Google Scholar 

  • Rapaport MH, Wolkow R, Rubin A, Hackett E, Pollack M, Ota KY (2001) Sertraline treatment of panic disorder: results of a long-term study. Acta Psychiatr Scand 104:289–298

    Article  PubMed  CAS  Google Scholar 

  • Rickels K, Pollack MH, Sheehan DV, Haskins JT (2000) Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 157:968–974

    Article  PubMed  CAS  Google Scholar 

  • Rickels K, Mangano R, Khan A (2004) Double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder. J Clin Psychopharmacol 24:488–496

    Article  PubMed  CAS  Google Scholar 

  • Roy-Byrne PP, Wagner AW, Schraufnagel TJ (2005) Understanding and treating panic disorder in the primary care setting. J Clin Psychiatry 66(Suppl 4):16–22

    PubMed  Google Scholar 

  • Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, Derivan AT (1998) A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry 59:116–122

    PubMed  CAS  Google Scholar 

  • Sasson Y, Iancu I, Fux LF, Taub M, Dannon PN, Zohar J (1999) A double-blind crossover comparison of clomipramine and desipramine in the treatment of panic disorder. Eur Neuropsychopharmacol 9:191–196

    Article  PubMed  CAS  Google Scholar 

  • Seedat S, van Rheede VO, Muller JE, Mohr N, Stein DJ (2003) Reboxetine and citalopram in panic disorder: a single-blind, cross-over, flexible-dose pilot study. Int Clin Psychopharmacol 18:279–284

    Article  PubMed  Google Scholar 

  • Sharp DM, Power KG, Simpson RJ, Swanson V, Anstee JA (1997) Global measures of outcome in a controlled comparison of pharmacological and psychological treatment of panic disorder and agoraphobia in primary care. Br J Gen Pract 47:150–155

    PubMed  CAS  Google Scholar 

  • Shear M, Brown TA, Barlow DH, Money R, Sholomskas DE, Woods SW, Gorman JM, Papp LA (1997) Multicenter collaborative panic disorder severity scale. Am J Psychiatry 154:1571–1575

    PubMed  CAS  Google Scholar 

  • Sheehan DV (1983) The anxiety disease. Charles Scribners Sons, New York, NY

    Google Scholar 

  • Sheehan DV, Burnham DB, Iyengar MK, Perera P (1983) Lack of efficacy of a new antidepressant (bupropion) in the treatment of panic disorder with phobias. J Clin Psychopharmacol 3:28–31

    Article  PubMed  CAS  Google Scholar 

  • Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    PubMed  Google Scholar 

  • Sheehan DV, Burnham DB, Iyengar MK, Perera P (2005) Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder. J Clin Psychiatry 66:34–40

    Article  PubMed  CAS  Google Scholar 

  • Simon NM, Emmanuel N, Ballenger J, Worthington JJ, Kinrys G, Korbly NB, Farach FJ, Pollack MH (2003) Bupropion sustained release for panic. Psychopharmacol Bull 37:66–72

    PubMed  Google Scholar 

  • Smith D (2001) The efficacy and tolerability of venlafaxine compared with other antidepressants in depression: a meta-analysis. J Psychopharmacol 15:A11

    Google Scholar 

  • Stahl SM, Gergel I, Li D (2003) Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 64:1322–1327

    Article  PubMed  CAS  Google Scholar 

  • Thase ME, Entsuah AR, Rudolph RL (2001) Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 178:234–241

    Article  PubMed  CAS  Google Scholar 

  • Tiller JW, Bouwer C, Behnke K (1999) Moclobemide and fluoxetine for panic disorder. International Panic Disorder Study Group. Eur Arch Psychiatry Clin Neurosci 249(Suppl 1):7–10

    Google Scholar 

  • Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M (2002) Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. J Clin Psychiatry 63:31–37

    PubMed  CAS  Google Scholar 

  • Wade AG, Lepola U, Koponen HJ, Pedersen V, Pedersen T (1997) The effect of citalopram in panic disorder. Br J Psychiatry 170:549–553

    Article  PubMed  CAS  Google Scholar 

  • Weissman MM (1991) Panic disorder: impact on quality of life. J Clin Psychiatry 52:6–8

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Michael Rennert, PhD for his editorial assistance on this manuscript. Funding for this study was provided by Wyeth Research, Collegeville, Pennsylvania.

Disclosures

Mark Pollack, MD

Advisory boards and consultation

AstraZeneca, Brain Cells, Bristol Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Eli Lilly, Medavante, Neurocrine, Neurogen, Novartis, Otsuka Pharmaceuticals, Pfizer, Predix, Roche, Laboratories, Sanofi, Sepracor, Solvay, Tikvah Therapeutics, Transoral Pharmaceuticals, UCB Pharma, Wyeth

Research grants

Bristol Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, NIDA NIMH, Pfizer, Sepracor, UCB Pharma, Wyeth

Speaker programs

Bristol Myers Squibb, Forest Laboratories, GlaxoSmithKline, Janssen, Lilly, Pfizer, Solvay, Wyeth

Equity

Medavante, Mensante

Naomi Simon, MD, MSc

Research support

Astra Zeneca, Cephalon, Forest Laboratories, Glaxo SmithKline, Janssen, Eli Lilly Inc., NARSAD, NIMH, Pfizer, Inc., UCB- Pharma, Sepracor

Advisory/consulting

Paramount Biosciences, Solvay

Speaking

Forest Laboratories, Janssen, Eli Lilly Inc., Pfizer, Inc., UCB- Pharma, Sepracor

Richard Entsuah, PhD and Evan Tzanis are employees of Wyeth. Richard Mangano, PhD is a former Wyeth employee but was an employee of Wyeth at the time the study was conducted and the manuscript was written.

All authors confirm that they have provided significant input in the study design, collection, analysis, and interpretation of data and writing the reports. They have had full control of all primary data and agree to allow the journal to review the data if requested.

Author information

Authors and Affiliations

  1. Massachusetts General Hospital, Simches Research Building, 185 Cambridge Street, Suite 2200, 2nd Floor, Boston, MA, 02114-2790, USA

    Mark Pollack & Naomi M. Simon

  2. Wyeth Research, Collegeville, PA, USA

    Richard Mangano, Richard Entsuah & Evan Tzanis

Authors
  1. Mark Pollack
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Mangano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard Entsuah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Evan Tzanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naomi M. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Pollack.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-007-1011-9

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pollack, M., Mangano, R., Entsuah, R. et al. A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder. Psychopharmacology 194, 233–242 (2007). https://doi.org/10.1007/s00213-007-0821-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-0821-0

Keywords

Search

Navigation